n-3 polyunsaturated fatty acids suppress the localization and activation of signaling proteins at the immunological synapse in murine CD4+ T cells by affecting lipid raft formation.
The molecular properties of immunosuppressive n-3 polyunsaturated fatty acids (PUFA) have not been fully elucidated. Using CD4(+) T cells from wild-type control and fat-1 transgenic mice (enriched in n-3 PUFA), we show that membrane raft accumulation assessed by Laurdan (6-dodecanoyl-2-dimethyl aminonaphthalene) labeling was enhanced in fat-1 cells following immunological synapse (IS) formation by CD3-specific Ab expressing hybridoma cells. However, the localization of protein kinase Ctheta, phospholipase Cgamma-1, and F-actin into the IS was suppressed. In addition, both the phosphorylation status of phospholipase Cgamma-1 at the IS and cell proliferation as assessed by CFSE labeling and [(3)H]thymidine incorporation were suppressed in fat-1 cells. These data imply that lipid rafts may be targets for the development of dietary agents for the treatment of autoimmune and chronic inflammatory diseases.
Kim
Wooki
W
Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA.
Fan
Yang-Yi
YY
Barhoumi
Rola
R
Smith
Roger
R
McMurray
David N
DN
Chapkin
Robert S
RS
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D044943:Fatty Acid Desaturases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000502:physiology*; D054992:Immunological Synapses / Q000737:chemistry / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D021962:Membrane Microdomains / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D010766:Phosphorylation / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
D029742:Caenorhabditis elegans Proteins; D015525:Fatty Acids, Omega-3; D047908:Intracellular Signaling Peptides and Proteins; C466741:fat-1 protein, C elegans; D044943:Fatty Acid Desaturases